Adult: For the treatment of moderate to severe cases: Initially, 100 mg or 200 mg once daily. Adjust dose based on tolerability and efficacy; consider dose reduction in patients receiving 200 mg after disease control is achieved. Max: 200 mg daily. Consider discontinuation of treatment if there is no evidence of therapeutic benefit after 12 weeks. Do not initiate treatment in patients with platelet count <150 x 103/mm3, absolute lymphocyte count (ALC) <0.5 x 103/mm3, absolute neutrophil count (ANC) <1 x 103/mm3, or Hb value <8 g/dL. Dosing interruption or discontinuation may be required if serious or opportunistic infection occurs or according to the patient's laboratory abnormalities (refer to specific product guidelines). Child: 12-17 years For the treatment of moderate to severe cases: Initially, 100 mg once daily. Max: 200 mg daily. Elderly: ≥65 years For the treatment of moderate to severe cases: Initially, 100 mg once daily. Max: 200 mg daily.
Special Patient Group
Patients receiving strong CYP2C19 inhibitors (e.g. fluvoxamine, fluoxetine, fluconazole, ticlopidine): Reduce to 50 mg or 100 mg once daily.
Pharmacogenomics:
Abrocitinib is metabolised mainly by CYP2C19 into active metabolites, 3-hydroxypropyl and 2-hydroxypropyl. Patients who have little to no CYP2C19 isoenzyme function are called poor metabolisers. The prevalence of CYP2C19 poor metabolisers is approx 3-5% in Caucasians and Blacks, and 15-20% in Asians. Following a single dose, abrocitinib exposure was 2.3-fold higher in CYP2C19 poor metabolisers as compared to those who are normal metabolisers. The clinical significance of this change is uncertain but some product labelling of abrocitinib recommends dose reduction in patients who are CYP2C19 poor metabolisers. Genetic testing may also be considered.
Based on the annotation of the US Food and Drug Administration (US FDA) drug label for abrocitinib, in patients who are known or suspected to be CYP2C19 poor metabolisers, the initial recommended dose of abrocitinib is 50 mg once daily. If there is no adequate response after 12 weeks, may consider increasing the dose to 100 mg once daily; discontinue treatment if the response is inadequate after the dose increase.
Renal Impairment
eGFR <30 mL/min/1.73 m2: Initially, 50 mg once daily. Max: 100 mg daily. eGFR 30 to <60 mL/min/1.73 m2: Reduce to 50 mg or 100 mg once daily.
Hepatic Impairment
Severe (Child-Pugh class C): Contraindicated.
Administration
May be taken with or without food. Swallow whole w/ water, do not crush/split/chew. Take at approx the same time each day.
Contraindications
Active serious systemic infections (including TB). Severe hepatic impairment. Pregnancy and lactation. Concomitant use with antiplatelet therapy (except for low dose of aspirin [≤81 mg daily]) during the 1st 3 months of treatment.
Special Precautions
Patient with chronic or recurrent infection, history of serious or opportunistic infection, underlying condition predisposing to infection; risk factors for DVT or pulmonary embolism (e.g. obesity, history of DVT or pulmonary embolism, undergoing major surgery, prolonged immobilisation); CV risk factors; known malignancy (apart from successfully treated non-melanoma skin cancer or cervical cancer in situ) or who develops malignancy during treatment. Patient who has been exposed to TB or who has travelled or resided in areas where mycoses or TB are endemic. Patient receiving moderate or strong inhibitors of both CYP2C19 and CYP2C9, or moderate or strong inducers of CYP2C19 or CYP2C9. Avoid administration of live, attenuated vaccines immediately before, during, and immediately after treatment with abrocitinib. Current or past smokers. CYP2C19 poor metabolisers. Moderate to severe renal impairment. Children and elderly.
PO: Z (Animal studies showed dystocia, embryo-foetal lethality and foetal skeletal variations. Should be avoided during pregnancy or contraindicated (manufacturer specific).)
Patient Counseling Information
This drug may cause dizziness, if affected, do not drive or operate machinery. Women of childbearing potential must use effective contraception during therapy and for 1 month after the last dose.
Monitoring Parameters
Screen patients for TB or viral hepatitis before initiating treatment and periodically thereafter. Consider annual screening for patients in highly endemic areas for TB. Monitor CBC and lipid panel at baseline, 4 weeks after starting therapy, and periodically thereafter as clinically indicated. Perform periodic skin examinations, particularly in patients who are at increased risk for skin cancer. Assess for signs and symptoms of infection (during and after therapy) or thrombosis.
Drug Interactions
Increased abrocitinib active moiety exposures with CYP2C19 or CYP2C9 inhibitors (e.g. fluvoxamine, fluconazole). Reduced abrocitinib active moiety exposures with CYP2C19 or CYP2C9 inducers (e.g. rifampicin). May increase the serum concentration of dabigatran. Potentially Fatal: Concomitant use with antiplatelet agents may increase the risk of bleeding with thrombocytopenia.
Action
Description: Abrocitinib is a Janus kinase (JAK) inhibitor that is selective for JAK1. It reversibly inhibits JAK1 by blocking the ATP binding site which prevents the signalling of interleukin-4, interleukin-13, and other cytokines involved in the pathogenesis of atopic dermatitis. Pharmacokinetics: Absorption: Rapidly and well absorbed. Bioavailability: Approx 60%. Time to peak plasma concentration: Within 1 hour. Distribution: Volume of distribution: Approx 100 L. Plasma protein binding: Approx 64%, mainly to albumin. Metabolism: Metabolised in the liver mainly by CYP2C19 and CYP2C9 isoenzymes and to a lesser extent by CYP3A4 and CYP2B6 isoenzymes into 2 active metabolites, M1 (3-hydroxypropyl) and M2 (2-hydroxypropyl). Excretion: Via urine (mainly as active metabolites; <1% as unchanged drug). Elimination half-life: 3-5 hours (abrocitinib and active metabolites).
Chemical Structure
Abrocitinib Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 78323835. https://pubchem.ncbi.nlm.nih.gov/compound/Abrocitinib. Accessed Oct. 28, 2022.
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